Phagocytes are blood cells that ingest and destroy other cells, microorganisms, and other foreign matter in the blood and tissues of animals. Monocyte/macrophages are phagocytes. Monocytes are immature cells that are produced in bone marrow and migrate into tissues and body cavities where they mature into macrophages. The monocyte/macrophage system plays a vital role in host defense mechanisms such as initiating and regulating immune responses; phagocytosing and killing microorganisms; exerting anti-tumor activities; phagocytosing and degrading effete cells, cellular debris, and other particulate matter; and secreting soluble biologically active substances. Given these functions, there has been considerable interest in finding substances that affect monocyte/macrophage activity.
In other unrelated work, there has been considerable research with respect to a group of proteins known as interferons. See generally E. Borden, 54 Cancer 2770-2776 (1984); E. Borden, Interferons And Cancer: How The Promise Is Being Kept, "Interferons", Vol. 5, Acad. Press 43-83 (1984). The disclosure of the above articles and of all other articles referred to herein are incorporated by reference as if fully set forth herein.
As a result of a large body research on the interferons, it has become clear that they induce the synthesis of many new proteins within cells they contact. It is also believed that some of the many proteins induced by the interferons must somehow mediate the interferon induced biological effects. However, the induced proteins' role in mediating the effects of interferons is unknown. See E. De Maeyer et al., "Interferons And Other Regulatory Cytokines", John Wiley And Sons (1988).
One interferon induced protein ("DA15") of about 15,000 daltons (about 156 amino acids) was isolated from the cytoplasm of a line of human lymphoblastoid cells after induction by interferon. Since then there have been reports on the purification to homogeneity of the protein, the isolation and location of the nucleotide sequence responsible for the protein, the amino acid sequence deduced from the cDNA therefor, particular portions of the gene responsible for transcription of the gene, and the mechanism that hosts use to modify a 17-kDa precursor (about 165 amino acids) ("DA17") of the protein. DA17 differs from DA15 in that DA17 has eight additional amino acids at the carboxy terminus. See B. Korant et al., 259 J. Bio. Chem. 14835-14839 (1984); D. Blomstrom et al., 261 J. Bio. Chem. 8811-8816 (1986); N. Reich et al., 84 P.N.A.S. USA 6394-6398 (1987); E. Knight et al., 263 J. Bio. Chem. 4520-4522 (1988 ). See N. Feltham et al., 9 J. Interf. Res. 493, 506 (1989). The art has to date been unable to determine the function of either DA15 or DA17.
Thus, it can be seen that a need exists for an improved means for stimulating a host defense mechanism by activating phagocytes.